Selinexor Combination Therapy for Multiple Myeloma

Not currently recruiting at 2 trial locations

Overseen By Kristin Ivanovski

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hackensack Meridian Health

Must be taking: Carfilzomib, Pomalidomide, Daratumumab

Must not be taking: Glucocorticoids

Disqualifiers: Smoldering MM, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Up to 30 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new combination of medicines, including selinexor (a nuclear export inhibitor), for people with multiple myeloma, a type of blood cancer, who haven't responded to their current treatment. Participants will be grouped based on their current treatment with carfilzomib, pomalidomide, or daratumumab. The trial aims to determine if adding selinexor can improve outcomes for those with progressing disease. This trial may suit patients whose multiple myeloma has worsened despite treatment with one of the specified drug regimens. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it seems you will continue with your current treatment regimen as part of the study. It's best to discuss this with your doctor to understand how your current medications fit into the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining selinexor with carfilzomib is generally safe and well-tolerated. Studies have found that patients with relapsed or refractory multiple myeloma, a type of blood cancer, responded well to this combination. Some side effects occurred, but they were manageable.

Similarly, the combination of selinexor with pomalidomide has been generally tolerable. In earlier studies, patients showed initial positive responses, and most side effects were manageable.

For the combination of selinexor with daratumumab, both drugs have FDA approval for treating multiple myeloma, indicating a level of safety. This combination has been tested in patients who have had many previous treatments, and it appeared safe for them, although side effects were noted.

Overall, while each combination may have its own potential side effects, earlier studies have considered them generally safe. Patients should talk with their doctors about what to expect during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they combine Selinexor with other medications to enhance effectiveness. Selinexor works by blocking proteins that cancer cells use to grow, which is different from many current treatments that primarily target the cancer cells directly. This novel mechanism could potentially improve outcomes when used alongside drugs like Carfilzomib, Pomalidomide, and Daratumumab. By integrating these combinations, there's hope for a more powerful attack on the cancer, offering new possibilities for patients who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will evaluate different selinexor combination therapies for multiple myeloma. Research has shown that combining selinexor with carfilzomib, one of the treatment arms in this trial, yields promising results for patients with multiple myeloma. Studies found this combination to be effective and well-tolerated, aiding patients whose disease did not respond to previous treatments. Another arm in this trial will test the pomalidomide-selinexor combination, with early data suggesting it works well in patients with resistant multiple myeloma. It is generally considered safe and shows signs of effectiveness. Lastly, the trial will explore the daratumumab-selinexor combination, which has been tested and may improve outcomes for those with hard-to-treat forms of the disease. Overall, these combinations show potential to help patients who have not had success with other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Noa Biran, MD

Principal Investigator

Hackensack Meridian Health

Are You a Good Fit for This Trial?

Adults with Multiple Myeloma showing disease progression on current treatments including carfilzomib, pomalidomide, or daratumumab can join. They must have good organ function and be able to follow the study's procedures. Pregnant women, those with serious health issues that could affect participation, recent recipients of certain therapies, or individuals with active infections cannot participate.

Inclusion Criteria

I am using effective birth control methods.

My kidney function is good as tested within the last 28 days.

Compliance with transfusion intervals and guidelines

Exclusion Criteria

You are not expected to live for more than 3 months.

I am unable or unwilling to take recommended supportive medications.

I do not have an active infection needing IV drugs within the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor in combination with carfilzomib, daratumumab, or pomalidomide on a 28-day cycle until progressive disease, death, toxicity, or withdrawal

Up to 30 months

Visits on days 1, 8, 15, and 22 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Pomalidomide
• Selinexor

Trial Overview The trial is testing Selinexor in combination with either Carfilzomib, Daratumumab or Pomalidomide in patients whose Multiple Myeloma has worsened despite treatment. It aims to see how well patients respond to this mix of drugs until they experience disease progression or unacceptable side effects.

How Is the Trial Designed?

Group I: Pomalidomide-containing Regimen Experimental Treatment 3 Interventions

Pomalidomide 4 mg po daily for 21 days. Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 60 mg on days 1, 8 and 15.

Group II: Exploratory/Daratumumab-containing Regimen Experimental Treatment 3 Interventions

Daratumumab on current schedule (16 mg/kg IV days 1, 8, 15 and 22 for cycles 1-2; days 1 and 15 for cycles 3-6; day 1 for cycle 7 and on). Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 100 mg on days 1, 8, 15 and 22.

Group III: Carfilzomib-containing Regimen Experimental Treatment 3 Interventions

Carfilzomib 56 mg/m2 on days 1, 8 and 15. Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 80 mg on days 1, 8 and 15.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Hackensack Meridian Health

Lead Sponsor

Trials

141

Recruited

42,900+

Karyopharm Therapeutics Inc

Industry Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34802051/

Once weekly selinexor, carfilzomib and dexamethasone in ... Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/10050/489159/Once-Weekly-Selinexor-Carfilzomib-and

Once Weekly Selinexor, Carfilzomib and Dexamethasone ... Efficacy endpoints included ORR, duration of response (DOR), PFS, overall survival (OS), and time to response (TTR). Results: Of the 33 patients ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7554

Updated results from phase 2b study of selinexor in ... This trial demonstrates that selinexor can restore sensitivity to regimens to which MM patients are actively refractory.

4. nature.com nature.com/articles/s41408-025-01256-2

Carfilzomib prescribing patterns and outcomes for relapsed ... Our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023001842

Selinexor-Based Triplet Regimens in Patients With Multiple ... Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6772147/

Phase 1 study of selinexor plus carfilzomib and ... Secondary objectives were to determine safety, tolerability and efficacy. Patients aged ≥18 years with progressive RRMM were enrolled at five Multiple Myeloma ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02628704

Study Details | NCT02628704 | Selinexor, Carfilzomib, and ... Double-blind study will compare the efficacy and assess safety of selinexor plus carfilzomib (Kyprolis®) plus low-dose dexamethasone versus placebo plus ...

8. investors.karyopharm.com investors.karyopharm.com/2020-12-07-Karyopharm-Presents-XPOVIO-R-Selinexor-Data-in-Multiple-Myeloma-and-Diffuse-Large-B-Cell-Lymphoma-at-the-American-Society-of-Hematology-2020-Annual-Meeting

Karyopharm Presents XPOVIO® (Selinexor) Data in ... These results suggest that SVd is an effective and safe regimen and, if approved, may be an important treatment option for patients with high ...